Adjunctive antiepileptic drug treatment can lower risk of dying from a sudden unexpected death

New research published online in The Lancet Neurology, found that epilepsy patients who receive additional treatment with anti-epileptic drugs (AEDs) have about a seven times lower risk of passing away from sudden unexpected death—the most common cause of death in epilepsy patients.

Sudden unexplained death is 20 times more common in people with epilepsy than in the general population. Research has identified some potentially preventable risk factors for sudden unexpected death in epilepsy (SUDEP) including a high number of generalized tonic-clonic seizures and taking multiple AEDs. But until now, no intervention has been assessed in a controlled study or shown to be beneficial at preventing SUDEP.

In this study, Philippe Ryvlin, Hôpital Neurologique, Lyon, France, and colleagues pooled data from 112 randomized trials of AED add-on treatment of adults with refractory epilepsy to compare the incidence of definite or probable SUDEP between patients receiving adjunctive AED therapy at effective doses and those given a placebo. A total of 33 deaths occurred in the trials, of which 18 deaths were deemed probable or definite SUDEP, and two deaths possible SUDEP.

Overall, analysis showed that patients treated with adjunctive AEDs at effective doses were about seven times less likely to pass away from SUDEP than patients given a placebo.

The authors suggest that the reduction in seizure frequency is the most likely explanation for the very low rate of SUDEP in patients given AEDs at effective doses. They point out that contrary to research suggesting that being on multiple AEDs (polytherapy) might increase the risk of SUDEP: “Our data suggest that add-on AEDs at doses effective on seizure frequency reduce the risk of SUDEP despite increasing the drug load, at least during the average 3-month duration of randomized trials.” They conclude: “This finding provides an argument not only for active revision and optimum management of treatment in patients with uncontrolled seizures, but also for further prospective and long-term investigation of this unsettled issue.”

Dale Hesdorffer from Columbia University, New York, USA and Torbjorn Tomson from the Karolinska Institute, Stockholm, Sweden, outline three key implications of the findings: “First, the study provides strong evidence for an effective intervention to reduce SUDEP risk. Second, the protective effect of adjunctive therapy suggests that seizure control could be extremely important for SUDEP prevention. Third, polytherapy does not increase risk of SUDEP during the time period of a randomized trial.”